α1-adrenoceptors down-regulate ClC-2 chloride channels in epithelial cells from the acutely denervated jejunum

Acute sympathetic denervation of the small intestine up-regulates α1-adrenoceptors on villus enterocytes and activation of these α1-adrenoceptors inhibits chloride secretion. We tested whether α1-adrenoceptor-mediated inhibition of chloride secretion was the result of reduced ClC-2 chloride channel expression. Phorbol myristate acetate (PMA) (a protein kinase C (PKC) activator) had no effect on ClC-2 levels. In contrast, α1-adrenoceptor activation significantly decreased ClC-2 protein levels in both the villus (1.58 ± 0.19 to 0.75 ± 0.19 arbitrary units) and crypt (1.69 ± 0.15 to 0.37 ± 0.23 arbitrary units) epithelial cells from the acutely denervated jejunum but not innervated controls. These data suggest that inhibition of chloride secretion following α1-adrenoceptor activation in the acutely denervated small intestine may be through ClC-2 down-regulation.